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AMPLIFICATION OF CCL4 TOXICITY BY CHLORDECONE: DESTRUCTION OF RAT HEPATIC MICROSOMAL CYTOCHROME P-450 SUBPOPULATION
Citation:
Chaudhury, S. AND H. Mehendele. AMPLIFICATION OF CCL4 TOXICITY BY CHLORDECONE: DESTRUCTION OF RAT HEPATIC MICROSOMAL CYTOCHROME P-450 SUBPOPULATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/052.
Description:
Previous work has shown that chlordecone (CD)-amplified CCl4 hepatoxicity and lethality can be mitigated by pretreatment with (+)-cyanidanol. hese studies also revealed that stimulated hepatocellular regeneration might play an important role in the cyanidanol protection of CD amplified CC14 toxicity. he present studies conducted over a time course of 0 to 120 hr after CC14 challenge describe sequential changes in hepatic [3H]-thymidine incorporation into hepatocellular nuclear DNA, polyamines and related enzymes, and histomorphometry of liver sections from variously treated rats. ale Sprague-Dawley rats (125-150 g) were maintained on a control diet or on a diet contaminated with CD (10 ppm for 15 days) and/or pretreated with cyanidanol (250 mg/kg, ip) at 48, 24 and 2 hr before a single ip injection of 50 ul CCl4/kg(L) to 100 ul CCl4/kg(H) on day 16 of the dietary protocol. yanidanol pretreatment significantly stimulated the hepatic [3tt]thymidine incorporation into hepatocellular nuclear DNA of control rats irrespective of CD pretreatment. imilarly, polyamine metabolism was altered favorably for cell division, although mitotic index (metaphase) was not increased. yanidanol-stimulated [3H]-thymidine incorporation was highly suppressed in rats receiving the CD + CC14(H) combination treatment up to 36 hr, but after this time point a marked increase was observed. epatocellular regeneration, quantified histomorphometrically as volume density of cells in metaphase was progressively increased in rats protected from CD + CC14 interaction by cyanidanol, starting at 36 hr and lasting until 72 hr.